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During emergency evacuation, it is crucial to accurately detect and classify different groups of evacuees based on their behaviours using computer vision. Traditional object detection models trained on standard image databases often fail to recognise individuals in specific groups such as the elderly, disabled individuals and pregnant women, who require additional assistance during emergencies. To address this limitation, this study proposes a novel image dataset called the Human Behaviour Detection Dataset (HBDset), specifically collected and annotated for public safety and emergency response purposes. This dataset contains eight types of human behaviour categories, i.e. the normal adult, child, holding a crutch, holding a baby, using a wheelchair, pregnant woman, lugging luggage and using a mobile phone. The dataset comprises more than 1,500 images collected from various public scenarios, with more than 2,900 bounding box annotations. The images were carefully selected, cleaned and subsequently manually annotated using the LabelImg tool. To demonstrate the effectiveness of the dataset, classical object detection algorithms were trained and tested based on the HBDset, and the average detection accuracy exceeds 90 %, highlighting the robustness and universality of the dataset. The developed open HBDset has the potential to enhance public safety, provide early disaster warnings and prioritise the needs of vulnerable individuals during emergency evacuation.

Inefficient drug penetration hurdled by the stroma in the tumor tissue leads to a diminished therapeutic effect for drugs and a reduced infiltration level of immune cells. Herein, we constructed a PEGylated dendritic epirubicin (Epi) prodrug (Epi-P4D) to regulate the metabolism of cancer-associated fibroblasts (CAFs), thus enhancing Epi penetration into both multicellular tumor spheroids (MTSs) and tumor tissues in mouse colon cancer (CT26), mouse breast cancer (4T1) and human breast cancer (MDA-MB-231) models. Enhanced cytotoxicity against CT26 MTSs and remarkable antitumor efficacy of Epi-P4D were ascribed to reduced fibronectin, α-SMA, and collagen secretion. Besides, thinning of the tumor tissue stroma and efficient eradication of tumor cells promoted the immunogenic cell death effect for dendritic cell (DC) maturation and subsequent immune activation, including elevating the CD4+ T cell population, reducing CD4+ and CD8+ T cell hyperactivation and exhaustion, and amplifying the natural killer (NK) cell proportion and effectively activating them. As a result, this dendritic nanomedicine thinned the stroma of tumor tissues to enhance drug penetration and facilitate immune cell infiltration for elevated antitumor efficacy.

Our focus in this study was on examining the convergence problem of a novel method, inspired by the Ulm-Chebyshev-like Cayley transform method, which was designed to solve the inverse eigenvalue problems (IEPs) with multiple eigenvalues. Compared with other existing methods, the proposed method has higher convergence order and/or requires less operations. Under the assumption that the relative generalized Jacobian matrices at a solution are nonsingular, the proposed method was proved to be convergent with cubic convergence. Experimental findings demonstrated the practicality and efficiency of the suggested approaches.

Objective: To investigate whether melatonin (MT) secretion in different parts of the gastrointestinal tract (GIT) exhibits seasonal variations and its correlation with immune regulation. Methods: Sixty Sprague-Dawley rats were divided into control and model groups, and the pineal gland was removed in the model group. Stomach, jejunum, ileum, and colon tissues were obtained during the spring equinox, summer solstice, beginning of autumn, autumn equinox, and winter solstice. The levels of MT, MT receptors (MR), arylalkylamine N-acetyltransferase (AANAT), hydroxyindole-O-methyltransferase (HIOMT), interleukin-2 (IL-2), and interleukin-10 (IL-10) in the GIT were measured using enzyme-linked immunosorbent assay. Results: Except for the stomach, the jejunum, ileum, and the colon showed seasonal tendencies in MT secretion. In the control group, MT secretion in the jejunum and ileum was the highest in the long summer, and colonic MT secretion was the highest in winter. In the model group, MT levels in the colon were highest in the summer. The seasonal rhythms of the MR, AANAT, HIOMT, IL-2, and IL-10 in the colon were roughly similar to those of MT, and changed accordingly after pinealectomy. Conclusions: Gastrointestinal MT secretion is related to seasonal changes, and MT secretion in each intestinal segment is influenced by different seasons. The biological effects of MT in the gut are inextricably linked to the mediation of MR, and a hormone-receptor linkage exists between MT and MR. The effect of seasonal changes on the gastrointestinal immune system may be mediated through the regulation of seasonal secretion of MT.

At present, the controllable parameters of micro turbojet engines in engineering applications are mainly speed-fuel flow (hereinafter referred to as flow) control, in which closed-loop proportional–integral–derivative (PID) control is mostly used to achieve a stable control of engine speed under slow engine conditions. For the optimal adjustment of PID parameters, this paper designs an improved evolutionary strategy for the self-tuning of control parameters in the engine speed and flow control system and formulates an improved PI controller based on a neural network. The simulation experimental results show that the method can realistically achieve stable and fast control of the engine under above slow conditions.

How do transportation upgrades affect structural transformation in the labor market in developing countries? We focus on a specific case, Benin’s Djougou-N’dali Road Improvement Project conducted between 2004 and 2010, and estimate its effects on changes in the composition of workers by sector. Our difference-in-differences estimates suggest evidence of structural transformation in the labor market: the road improvement project leads to a relative increase in the proportion of workers in the industrial sector by 3.9 percentage points, representing a 30-percent increase. This is accompanied by a sharp decrease in the proportion of agricultural workers and an overall insignificant decrease in the proportion of service workers. These labor market effects are spatially heterogeneous: changes in agricultural workers and service workers are significant only in rural and urban areas, respectively, while both two types of areas see an increase in the proportion of industrial workers. Besides, these effects are significant only for female workers. Our findings present direct labor market effects of transportation upgrades through job switches across sectors, while other labor market mechanisms cannot explain structural transformation.

ABSTRACTThe rising prevalence and detrimental impact of inflammatory diseases have spurred the exploration of novel therapeutic approaches to tackle these conditions. Fuzi, lateral root of Aconitum carmichaelii Debx. has been used as a traditional Chinese medicine (TCM) for the treatment of inflammatory diseases for a long time. This article provides a comprehensive review of the medicinal applications, anti-inflammatory constituents, analytical techniques for detecting anti-inflammatory components, molecular mechanisms, and anti-inflammatory effects of Fuzi and its formulas. The information on Fuzi was collected from a variety of resources including classical works on Chinese herbal medicine, scientific databases (PubMed, Google Scholar, ACS, Web of Science, Science Direct, CNKI), TCMSP, NCBI, PubChem databases and others. About 122 compounds were isolated and identified from Fuzi, with alkaloids constituting the primary constituents that demonstrate potent anti-inflammatory activity. Specifically, among the identified compounds, there was one C-18 type, nineteen C-19 type, four C-20 type diterpenoid alkaloids, one other alkaloid, and 6 non-alkaloid constituents, all of which exhibited noteworthy anti-inflammatory and pain-alleviating properties in both in vivo and in vitro models of inflammation. These effects were mainly attributed to the reduction of pro-inflammatory cytokines, including IL-1, TNF-α, NO, IL-Iβ, and IL-6, as well as the inhibition of MAPK, NF-κB or PI3K/Akt signaling pathways, which effectively suppressed the inflammatory response and alleviated pain. Additionally, the anti-inflammatory effects were also achieved through the regulation of TLR4 expression and its downstream factors, or by modulating the homeostasis of the gut microbiota.

Abstract Purpose Since May 2022, Mpox has spread extensively outside of Africa, posing a serious threat to the health of people globally, and particularly to the men who have sex with men (MSM) population. Chongqing, a province in Southwest China, has relatively large MSM and people living with HIV (PLWH) populations, presenting conditions conducive to the wide dissemination of Mpox. In this study, we investigated the clinical characteristics of Mpox patients among MSM and PLWH in Chongqing, aiming to inform the development of targeted prevention, control, and treatment strategies for Mpox. Method We evaluated the clinical characteristics, travel history, time of onset, distribution and number of skin lesions of Mpox patients admitted to the Chongqing Public Health Medical Center between September 2022 and October 2023. Meanwhile, a series of clinical samples were collected and the pathogen of interest was identified as Mpox virus using quantitative polymerase chain reaction (qPCR). The results were presented in the form of cycle thresholds (Ct), which help to approximate the quantification of viral load. Results As of October 11, 2023, the Chongqing Public Health Medical Center reported a total of nine Mpox virus infections. All the patients identified were male and belonged to the MSM population, among whom seven (77.8%) were living with HIV, and maintained a preserved immune system while achieving viral suppression via effective ART. We observed no discernible clinical differences between MSM with Mpox with or without HIV, and no fatalities were recorded. Viral loads were observed to be higher in samples taken from the skin than those from the throat, nasopharynx, blood, or semen. Conclusion In this retrospective study, the clinical manifestations of MPXV infection appeared consistent among MSM patients, regardless of HIV status. Elevated MPXV viral loads in the skin and mucosal tissues, particularly at genital and anal sites, indicate that transmission is more likely to occur via direct physical contact as opposed to respiratory pathways or through exposure to bodily fluids.

Abstract Background Liguzinediol (Lig) has emerged as a promising candidate for mitigating Doxorubicin (DOX)-induced cardiotoxicity, a significant limitation in the clinical application of this widely used antineoplastic drug known for its efficacy. This study aimed to explore the effects and potential mechanisms underlying Lig’s protective role against DOX-induced cardiotoxicity. Methods C57BL/6 mice were treated with DOX. Cardiac function changes were observed by echocardiography. Cardiac structure changes were observed by HE and Masson staining. Immunofluorescence was applied to visualize the cardiomyocyte apoptosis. Western blotting was used to detect the expression levels of AMP-activated protein kinase (AMPK), sirtuin 3 (SIRT3), Caspase-3 and gasdermin E N-terminal fragment (GSDME-N). These experiments confirmed that Lig had an ameliorative effect on DOX-induced cardiotoxicity in mice. Results The results demonstrated that Lig effectively countered myocardial oxidative stress by modulating intracellular levels of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Lig reduced levels of creatine kinase (CK) and lactate dehydrogenase (LDH), while ameliorating histopathological changes and improving electrocardiogram profiles in vivo. Furthermore, the study revealed that Lig activated the AMPK/SIRT3 pathway, thereby enhancing mitochondrial function and attenuating myocardial cell apoptosis. In experiments with H9C2 cells treated with DOX, co-administration of the AMPK inhibitor compound C (CC) led to a significant increase in intracellular ROS levels. Lig intervention reversed these effects, along with the downregulation of GSDME-N, interleukin-1β (IL-1β), and interleukin-6 (IL-6), suggesting a potential role of Lig in mitigating Caspase-3/GSDME-mediated pyroptosis. Conclusion The findings of this study suggest that Lig effectively alleviates DOX-induced cardiotoxicity through the activation of the AMPK/SIRT3 pathway, thereby presenting itself as a natural product with therapeutic potential for preventing DOX-associated cardiotoxicity. This novel approach may pave the way for the development of alternative strategies in the clinical management of DOX-induced cardiac complications.

Abstract The aim of this study was to determine the role of lncRNA PART1 and downstream FUT6 in tumorigenesis and progression of head and neck cancer (HNC). Bioinformatics analysis and qRT-PCR revealed that lncRNA PART1 was expressed at low levels in HNC patients. The proliferation, apoptosis, migration and flow cytometry results showed that low expression of lncRNA PART1 inhibited apoptosis and promoted HNC cell migration and proliferation. In addition, animal experiments have also shown that low expression of lncRNA PART1 can promote tumor growth. LncRNA PART1 overexpression promoted apoptosis and inhibited HNC cell migration and proliferation. Through bioinformatics analysis, FUT6 was found to be expressed at low levels in HNC and to be correlated with patient survival. Immunohistochemical and qRT-PCR results revealed that FUT6 was underexpressed in tumour tissues and HNC cells. Cell and animal experiments showed that overexpression of FUT6 could inhibit tumour proliferation and migration. Bioinformatics analysis revealed that lncRNA PART1 was positively correlated with FUT6. By qRT-PCR and western blot, we observed that after knockdown of lncRNA PART1, both the mRNA and protein expression levels of FUT6 were reduced. The above results indicated that lncRNA PART1 and FUT6 play an important role in HNC, and that lncRNA PART1 affected the development of tumor by downstream FUT6.

Abstract Jinlida granule (JLD) is a Traditional Chinese Medicine (TCM) formula used for the treatment of type 2 diabetes mellitus (T2DM). However, the mechanism of JLD treatment for T2DM is not fully revealed. In this study, we explored the mechanism of JLD against T2DM by an integrative pharmacology strategy. Active components and corresponding targets were retrieved from Traditional Chinese Medicine System Pharmacology (TCMSP), SwissADME and Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine Database (BATMAN-TCM) database. T2DM-related targets were obtained from Drugbank and Genecards databases. The protein–protein interaction (PPI) network was constructed and analyzed with STRING (Search Toll for the Retrieval of Interacting Genes/proteins) and Cytoscape to get the key targets. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed with the Database for Annotation, Visualization and Integrated Discovery (DAVID). Lastly, the binding capacities and reliability between potential active components and the targets were verified with molecular docking and molecular dynamics simulation. In total, 185 active components and 337 targets of JLD were obtained. 317 targets overlapped with T2DM-related targets. RAC-alpha serine/threonine-protein kinase (AKT1), tumor necrosis factor (TNF), interleukin-6 (IL-6), cellular tumor antigen p53 (TP53), prostaglandin G/H synthase 2 (PTGS2), Caspase-3 (CASP3) and signal transducer and activator of transcription 3 (STAT3) were identified as seven key targets by the topological analysis of the PPI network. GO and KEGG enrichment analyses showed that the effects were primarily associated with gene expression, signal transduction, apoptosis and inflammation. The pathways were mainly enriched in PI3K-AKT signaling pathway and AGE-RAGE signaling pathway in diabetic complications. Molecular docking and molecular dynamics simulation verified the good binding affinity between the key components and targets. The predicted results may provide a theoretical basis for drug screening of JLD and a new insight for the therapeutic effect of JLD on T2DM.

Since the catalytic activity of most nanozymes is still far lower than the corresponding natural enzymes, there is urgent need to discover novel highly efficient enzyme-like materials. In this work, Co3V2O8 with hollow hexagonal prismatic pencil structures were prepared as novel artificial enzyme mimics. They were then decorated by photo-depositing Ag nanoparticles (Ag NPs) on the surface to further improve its catalytic activities. The Ag NPs decorated Co3V2O8 (ACVPs) showed both excellent oxidase- and peroxidase-like catalytic activities. They can oxidize the colorless 3,3’,5,5’-tetramethylbenzidine rapidly to induce a blue change. The enhanced enzyme mimetic activities can be attributed to the surface plasma resonance (SPR) effect of Ag NPs as well as the synergistic catalytic effect between Ag NPs and Co3V2O8, accelerating electron transfer and promoting the catalytic process. ACVPs were applied in constructing a colorimetric sensor, validating the occurrence of the Fenton reaction, and disinfection, presenting favorable catalytic performance. The enzyme-like catalytic mechanism was studied, indicating the chief role of ⋅O2- radicals in the catalytic process. This work not only discovers a novel functional material with double enzyme mimetic activity but also provides a new insight into exploiting artificial enzyme mimics with highly efficient catalytic ability.

Abstract Ensemble learning has the potential to enhance the efficacy of feeble classifiers significantly and is increasingly being utilized in Twitter bot detection. Previous methods have utilized stacking techniques to train the primary classifiers, implementing cross-validation to mitigate overfitting and enhance predictive accuracy. However, cross-validation substantially amplifies the computation time associated with stacking. To overcome this challenge, this paper presents a novel approach, the Simplified Stacking Graph Neural Network (SStackGNN), specifically designed for the detection of social bots. Our methodology leverages the power of Graph Neural Networks (GNNs) as base classifiers, enabling effective capturing of inter-account interactions. In addition, a Multilayer Perceptron (MLP) serves as a secondary classifier, amalgamating the outcomes of the foundational classifiers to generate final predictions, thereby enhancing the predictive performance of the GNNs. Instead of relying on cross-validation and distinct base classifier structures, we employ node-level, edge-level, and feature-level graph data augmentation techniques to acquire diverse foundational classifiers. This approach significantly alleviates the computational complexity while achieving superior performance. Experimental results demonstrate that our proposed SStackGNN outperforms other approaches.

Abstract Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.

Abstract Biodegradability is a crucial indicator to evaluate the sustainability of leather. Herein, a rapid method for biodegradation test in an aqueous medium by measuring biochemical oxygen demand was used to determine the biodegradability of leather from different tanning methods, tanning conditions and process stages. In addition, the difference in biodegradability between leather and leather-like synthetic materials were investigated. Chrome-free tanned leather showed higher degree of biodegradation and faster biodegradation rate than chrome tanned leather. Among them, leathers tanned with biomass-based tanning agents were much easier to biodegrade because the crosslinking network of tanned leather constructed with biomass was more susceptible to microbial attack. The enhancement of tanning effects through changing tanning methods and conditions (such as tanning agent dosage, pH and temperature) resulted in the decline of leather biodegradability. Future development of novel chrome-free tanning technologies should balance between these two aspects. The biodegradability of leather from tanning to post-tanning to finishing showed a stepwise decrease because various chemicals were applied and bound to leather during processing. Even so, finished leather still possessed significantly higher biodegradability compared to leather-like PU and microfiber synthetic materials, demonstrating superior environmental sustainability of natural leather. The results are expected to provide support for the evaluation of the ecological properties of leather and green upgrade of the leather industry. Graphical abstract

Scale effects significantly affect the rationality and accuracy of ecological models, so temporal and spatial scales are included in the construction and application of ecological studies. However, few ecological pattern analyses focus on both of these scales simultaneously, which is especially important in terms of synchrony. In this study, based on fishery catch data and simulated data, we propose a framework for coupled space-time scale analysis and reveal possible deficiencies in conventional scale studies. We verified the feasibility and reliability of the scheme using simulated data with different combinations of temporal and spatial scales. The results showed that our scheme can simultaneously identify and localize scale features in the variation in species spatial-temporal patterns, specifically regarding the synchrony and amplitude of temporal dynamics (or spatial patterns) of multiple sites (or times). Our scheme revealed that spatial scales had an important effect on the intrinsic 13-year scale features, which significantly improved our understanding of global Rajiformes fishery dynamics. This showed that the spatial-temporal patterns and scale features obtained based on the coupled space-time scale analysis were complete and more accurate. At the same time, our scheme correctly identified complex pattern structures, such as data stratification and multiple combinations of time and space scales, which can reduce possible errors in practical applications. This scheme can be applied to the identification and prediction of the spatial-temporal patterns in biodiversity in the future and will help in formulating effective policies promoting sustainable fishery resources management and comprehensive conservation of endangered marine species.

Background: Microglia-mediated inflammation is a critical factor in the progression of ischemic stroke. Consequently, mitigating excessive microglial activation represents a potential therapeutic strategy for ischemic injury. Thymol, a monophenol derived from plant essential oils, exhibits diverse beneficial biological activities, including anti-inflammatory and antioxidant properties, with demonstrated protective effects in various disease models. However, its specific effects on ischemic stroke and microglial inflammation remain unexplored. Methods: Rodent transient middle cerebral artery occlusion (tMCAO) model was established to simulate ischemic stroke. TTC staining, modified neurological function score (mNSS), and behavioral tests were used to assess the severity of neurological damage. Then immunofluorescence staining and cytoskeleton analysis were used to determine activation of microglia. Lipopolysaccharide (LPS) was utilized to induce the inflammatory response of primary microglia in vitro. Quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and enzyme-linked immunosorbent assay (ELISA) were performed to exam the expression of inflammatory cytokines. And western blot was used to investigate the mechanism of the anti-inflammatory effect of thymol. Results: In this study, we found that thymol treatment could ameliorate post-stroke neurological impairment and reduce infarct volume by mitigating microglial activation and pro-inflammatory response (IL-1β, IL-6, and TNF-α). Mechanically, thymol could inhibit the phosphorylation of phosphatidylinositol-3-kinase (PI3K), sink serine/threonine kinase (Akt), and mammalian target of rapamycin (mTOR), thereby suppressing the activation of nuclear factor-κB (NF-κB). Conclusions: Our study demonstrated that thymol could reduce the microglial inflammation by targeting PI3K/Akt/mTOR/NF-κB signaling pathway, ultimately alleviating ischemic brain injury. These findings suggest that thymol is a promising candidate as a neuroprotective agent against ischemic stroke.

The prevalence of dyslipidemia is increasing, and it has become a significant global public health concern. Some studies have demonstrated contradictory relationships between urinary metals and dyslipidemia, and the combined effects of mixed urinary metal exposure on dyslipidemia remain ambiguous. In this study, we examined how individual and combined urinary metal exposure are associated with the occurrence of dyslipidemia. According to the data from the 2018–2019 baseline survey database of the China Multi-Ethnic Cohort (CMEC) Study, a population of 9348 individuals was studied. Inductively coupled plasmamass spectrometry (ICP-MS) was used to measure 21 urinary metal concentrations in the collected adult urinary samples. The associations between urinary metals and dyslipidemia were analyzed by logistic regression, weighted quantile sum regression (WQS), and quantile-based g-computation (qgcomp), controlled for potential confounders to examine single and combined effects. Dyslipidemia was detected in 3231 individuals, which represented approximately 34.6 % of the total population. According to the single-exposure model, Al and Na were inversely associated with the risk of dyslipidemia (OR = 0.95, 95 % CI: 0.93, 0.98; OR = 0.89, 95 % CI: 0.83, 0.95, respectively), whereas Zn, Ca, and P were positively associated (OR = 1.69, 95 % CI: 1.42, 2.01; OR = 1.12, 95 % CI: 1.06, 1.18; OR = 1.21, 95 % CI: 1.09, 1.34, respectively). Moreover, Zn and P were significantly positively associated even after adjusting for these metals, whereas Al and Cr were negatively associated with the risk of dyslipidemia. The results of the WQS and qgcomp analyses showed that urinary metal mixtures were positively associated with the risk of dyslipidemia (OR = 1.26, 95 % CI: 1.15, 1.38; OR = 1.09, 95 % CI: 1.01, 1.19). This positive association was primarily driven by Zn, P, and Ca. In the sensitivity analyses with collinearity diagnosis, interaction, and stratified analysis, the results remained, confirming the reliability of the study findings. In this study, the individual and combined effects of urinary Zn, P, and Ca on dyslipidemia were determined, which provided novel insights into the link between exposure to metals and dyslipidemia.

Temporomandibular joint osteoarthritis (TMJ-OA) is usually caused by increased friction at the joint interface, excessive release of inflammatory factors and catabolic enzymes, and free radical accumulation, which can lead to accelerated degradation and damage of cartilage. In this study, we develop a biological metabolism-inspired injectable hydrogel crosslinking by hydrazide modified hyaluronic acid (HA-HYD), aldehyde modified hyaluronic acid (HA-ALD), and ε-polylysine coated catalase-mimic nanozyme (mesoporous manganese cobalt oxide). Herein, this nanozyme-reinforced hydrogel with outstanding and durable reactive oxygen species (ROS) depletion capability and biocompatibility can alleviate the oxidative stress microenvironment, improve cell viability and proliferation, as well as up-regulate chondrogenic related gene expression and cartilage matrix formation of chondrocytes in vitro. Intra-articular administration of this engineered hydrogel can effectively scavenge endogenous over-expressed ROS to ameliorate the harsh microenvironment in the cavity of TMJ-OA. The nanozyme-reinforced hydrogel reduced proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and enhance anti-inflammatory cytokines (IL-10) expression, induced polarization of synovial macrophages towards M2 phenotype, alleviated structural damage to the cartilage and subchondral bone of the condyle, thus reducing cartilage matrix destruction and protect cartilage in osteoarthritis. In summary, the bioinspired nanozyme-reinforced hydrogels might be used as a promising ROS scavenger for treatment of TMJ-OA.

ObjectiveGastrointestinal dysfunction are often associated with type 2 diabetes mellitus (T2DM), a complicated metabolic illness. Contributing factors have been proposed, including genetic predisposition, gene environmental, and lifestyle interactions, but the pathophysiology remains unknown.MethodsWe aim to explore the possible causes behind gastrointestinal dysfunction caused by type 2 diabetes in this study. A comprehensive analysis of the gastric sinus metabolome, transcriptome, and proteome in db/db mice with gastrointestinal dysfunction was conducted.ResultsThe model group of mice had considerably lower small intestine propulsion and gastric emptying rates, higher blood glucose levels, and were significantly obese compared to the control group. We identified 297 genes, 350 proteins, and 1,001 metabolites exhibiting significant differences between db/db and control mice (p < 0.05). Moreover, multi-omics analysis revealed that the genes, proteins, and metabolites in the T2DM-induced gastroenteropathy mice group were involved in arachidonic acid metabolism, glycerophospholipid metabolism and vitamin digestion and absorption. Specifically, Cbr3, Etnppl, and Apob were the major mRNAs associated with T2DM-induced gastrointestinal dysfunction, while Cyp2b10, Cyp2b19, Pgs1, Gpat3, Apoa4, and Tcn2 were the major proteins associated with T2DM-induced gastrointestinal injury, and 16(R)-HET, 5-HETE, LysoPC (22:0), and Pantothenic acid were the major metabolites associated with T2DM-induced gastrointestinal disorders.ConclusionThe mechanism of action of diabetic gastroenteropathy may be related to vitamin digestion and absorption, glycerophospholipid metabolism, and arachidonic acid metabolism.

Abstract Patients with glycogen storage disease type Ib (GSD‐Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD‐Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo‐polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single‐cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper‐activation of the CCL4L2‐VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD‐Ib. Collectively, the microbiota‐driven pathomechanism of IBD is demonstrated in GSD‐Ib and revealed the active role of the CCL4L2‐VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2‐VISR axis may represent a potential therapy for GSD‐associated IBD.

Mitochondrial damage has a particular impact on the immune system and tumor microenvironment, which can trigger cell stress, an inflammatory response, and disrupt immune cell function, thus all of which can accelerate the progression of the tumor. Therefore, it is of essence to comprehend how the immune system function and the tumor microenvironment interact with mitochondrial dysfunction for cancer treatment. Preserving the integrity of mitochondria or regulating the function of immune cells, such as macrophages, may enhance the efficacy of cancer therapy. Future research should concentrate on the interactions among mitochondria, the immune system, and the tumor microenvironment to identify new therapeutic strategies.

The continuous process of urbanization and climate change has led to severe urban heat island (UHI) effects. Constructing parks with cooling capabilities is considered an effective measure to alleviate UHI effects. However, most studies only quantify the cooling effect from a maximum value perspective, lacking a measure of temperature diffusion in space. This study combines the perspectives of maximum value and accumulation to define a cold island index, quantifying the cooling effect of 40 urban parks in the main urban area of Xi'an city. The results show that, on average, urban parks can reduce the surrounding environment by approximately 2.3℃, with a cooling range of about 127.1ha, which is three times the park area. Different factors drive the measurement of the cooling effect using different cold island indexes, but all indexes are highly correlated with green space area. There are significant differences in the cooling effect among different types of parks, and overall, ecological parks have the best cooling effect. The directional spread of internal cold islands in parks is most related to park shape, while external spread is related to surrounding green spaces. The research results have practical value in the construction of parks with cooling effects and the sustainable development of cities in urban planning processes..

Abstract SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor progression. Aberrant glycosylation has been intricately linked with immune escape and tumor growth. SEMA7A is a highly glycosylated protein with five glycosylated sites. The underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are unclear. Here, we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma, and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides (Asn 105, 157, 258, 330, and 602) via a direct protein‒protein interaction. A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the cytomembrane. Cytokine EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8, whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal transition. Aberrant N-glycosylation of SEMA7A leads to the differentiation of CD8+ T cells along a trajectory toward an exhausted state, thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell death. Deglycosylation of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based immunotherapy. Finally, we also define RBM4, a splice regulator, as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative splicing. These findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.

Abstract Background Scedosporium apiospermum (S. apiospermum) belongs to the asexual form of Pseudallescheria boydii and is widely distributed in various environments. S. apiospermum is the most common cause of pulmonary infection; however, invasive diseases are usually limited to patients with immunodeficiency. Case presentation A 54-year-old Chinese non-smoker female patient with normal lung structure and function was diagnosed with pulmonary S. apiospermum infection by metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF). The patient was admitted to the hospital after experiencing intermittent right chest pain for 8 months. Chest computed tomography revealed a thick-walled cavity in the upper lobe of the right lung with mild soft tissue enhancement. S. apiospermum was detected by the mNGS of BALF, and DNA sequencing reads were 426. Following treatment with voriconazole (300 mg q12h d1; 200 mg q12h d2-d20), there was no improvement in chest imaging, and a thoracoscopic right upper lobectomy was performed. Postoperative pathological results observed silver staining and PAS-positive oval spores in the alveolar septum, bronchiolar wall, and alveolar cavity, and fungal infection was considered. The patient’s symptoms improved; the patient continued voriconazole for 2 months after surgery. No signs of radiological progression or recurrence were observed at the 10-month postoperative follow-up. Conclusion This case report indicates that S. apiospermum infection can occur in immunocompetent individuals and that the mNGS of BALF can assist in its diagnosis and treatment. Additionally, the combined therapy of antifungal drugs and surgery exhibits a potent effect on the disease.

Abstract Type 2 diabetes mellitus (T2DM) poses a significant global health burden. This is particularly due to its macrovascular complications, such as coronary artery disease, peripheral vascular disease, and cerebrovascular disease, which have emerged as leading contributors to morbidity and mortality. This review comprehensively explores the pathophysiological mechanisms underlying these complications, protective strategies, and both existing and emerging secondary preventive measures. Furthermore, we delve into the applications of experimental models and methodologies in foundational research while also highlighting current research limitations and future directions. Specifically, we focus on the literature published post-2020 concerning the secondary prevention of macrovascular complications in patients with T2DM by conducting a targeted review of studies supported by robust evidence to offer a holistic perspective.

Abstract Children are generally susceptible to COVID-19, and infection with COVID-19 may cause serious harm to children. COVID-19 vaccination is an effective way to prevent infection at present, and many factors affect children's COVID-19 vaccination. This study aimed to explore the effects of perceived social support and health literacy on hesitancy towards first and second vaccine dose. This cross-sectional study was conducted in the Minhang District of Shanghai, China, in October 2022. A total of 1150 parents of preschool children from 10 kindergartens participated. The survey encompassed four sections, capturing data on sociodemographic attributes, health literacy, perceived social support, and parental COVID-19 vaccine hesitancy. Health literacy was measured using a self-designed questionnaire consisting of four dimensions. Perceived social support was assessed using the MSPSS questionnaire. Hierarchical multiple logistic regression was used to examine the relationship between the independent variables and parental hesitancy towards the first and second doses of COVID-19 vaccine. Parental hesitancy rate for the first dose of the COVID-19 vaccine was 69.6%, and for the second dose, it was 33.1%. The final integrated model showed that parental hesitancy towards the first and the second dose of COVID-19 vaccine was associated with parental educational level, allergy in children, information decision-making and information comprehension ability, perceived social support from family and friends. Health literacy and perceived social support are influence factors for parental hesitancy towards COVID-19 vaccine for preschool children. The findings will provide insights for future intervention studies on COVID-19 vaccine hesitancy and inform the development of vaccination policies.

Abstract Background This study aims to assess the influence of early serum phosphate fluctuation on the short-term prognosis of sepsis patients. Methods This retrospective study used the Medical Information Mart for Intensive Care IV database to analyze serum phosphate levels in sepsis patients within 3 days of ICU admission. According to the absolute value of delta serum phosphate (the maximum value minus the minimum value of serum phosphorus measured within three days), the patients were divided into four groups, 0–1.3, 1.4–2.0, 2.1–3.1, and ≥ 3.2 mg/dl. Meanwhile, the direction of delta serum phosphate was compared. With the serum phosphate change group of 0–1.3 mg/dl as the reference group, the relationship between delta serum phosphate and in-hospital mortality and 28-day mortality was analyzed by multivariate Logistics regression analysis. Results The study involved 1375 sepsis patients. Serum phosphate changes (0–1.3, 1.4–2.0, 2.1–3.1, and ≥ 3.2 mg/dl) correlated with in-hospital and 28-day mortality variations (p = 0.005, p = 0.008). Much higher serum phosphate fluctuation elevated in-hospital and 28-day mortality. Compared to the 0–1.3 mg/dl change group, adjusted odds ratios (OR) in other groups for in-hospital mortality were 1.25 (0.86–1.81), 1.28 (0.88–1.86), and 1.63 (1.10–2.43), and for 28-day mortality were 1.21 (0.86–1.72), 1.10 (0.77–1.57), and 1.49 (1.03–2.19). Under the trend of increasing serum phosphate, the ORs of in-hospital mortality and 28-day mortality in ≥ 3.2 mg/dl group were 2.52 and 2.01, respectively. Conclusion In conclude, the delta serum phosphate ≥ 3.2 mg/dl was associated with in-hospital mortality and 28-day mortality in patients with sepsis.

Abstract Systemic immune monitoring is a crucial clinical tool for disease early diagnosis, prognosis and treatment planning by quantitative analysis of immune cells. However, conventional immune monitoring using flow cytometry faces huge challenges in large-scale sample testing, especially in mass health screenings, because of time-consuming, technical-sensitive and high-cost features. However, the lack of high-performance detection platforms hinders the development of high-throughput immune monitoring technology. To address this bottleneck, we constructed a generally applicable DNA framework signal amplification platform (DSAP) based on post-systematic evolution of ligands by exponential enrichment and DNA tetrahedral framework-structured probe design to achieve high-sensitive detection for diverse immune cells, including CD4+, CD8+ T-lymphocytes, and monocytes (down to 1/100 μl). Based on this advanced detection platform, we present a novel high-throughput immune-cell phenotyping system, DSAP, achieving 30-min one-step immune-cell phenotyping without cell washing and subset analysis and showing comparable accuracy with flow cytometry while significantly reducing detection time and cost. As a proof-of-concept, DSAP demonstrates excellent diagnostic accuracy in immunodeficiency staging for 107 HIV patients (AUC > 0.97) within 30 min, which can be applied in HIV infection monitoring and screening. Therefore, we initially introduced promising DSAP to achieve high-throughput immune monitoring and open robust routes for point-of-care device development.

Abstract Classical fungal mutant strains obtained by mutagenesis have helped to elucidate fundamental metabolic pathways in the past. In the filamentous fungus Neurospora crassa, the gluc-1 strain was isolated long ago and characterized by its low level of β-glucosidase activity, which is essential for the degradation of cellulose, the most abundant biopolymer on Earth and the main polymeric component of the plant cell wall. Based on genomic resequencing, we hypothesized that the causative mutation resides in the β-glucosidase gene gh3-3 (bgl6, NCU08755). In this work, growth patterns, enzymatic activities and sugar utilization rates were analyzed in several mutant and overexpression strains related to gluc-1 and gh3-3. In addition, different mutants affected in the degradation and transport of cellobiose were analyzed. While overexpression of gh3-3 led to the recovery of β-glucosidase activity in the gluc-1 mutant, as well as normal utilization of cellobiose, the full gene deletion strain Δgh3-3 was found to behave differently than gluc-1 with lower secreted β-glucosidase activity, indicating a dominant role of the amino acid substitution in the point mutated gh3-3 gene of gluc-1. Our results furthermore confirm that GH3-3 is the major extracellular β-glucosidase in N. crassa and demonstrate that the two cellodextrin transporters CDT-1 and CDT-2 are essential for growth on cellobiose when the three main N. crassa β-glucosidases are absent. Overall, these findings provide valuable insight into the mechanisms of cellulose utilization in filamentous fungi, being an essential step in the efficient production of biorefinable sugars from agricultural and forestry plant biomass.

Abstract Two-dimensional (2D) materials have drawn immense interests in scientific and technological communities, owing to their extraordinary properties and their tunability by gating, proximity, strain and external fields. For electronic applications, an ideal 2D material would have high mobility, air stability, sizable band gap, and be compatible with large scale synthesis. Here we demonstrate air stable field effect transistors using atomically thin few-layer PdSe2 sheets that are sandwiched between hexagonal BN (hBN), with large saturation current > 350 μA/μm, and high field effect mobilities of ~ 700 and 10,000 cm2/Vs at 300 K and 2 K, respectively. At low temperatures, magnetotransport studies reveal unique octets in quantum oscillations that persist at all densities, arising from 2-fold spin and 4-fold valley degeneracies, which can be broken by in-plane and out-of-plane magnetic fields toward quantum Hall spin and orbital ferromagnetism.

The application of Mg-based electrochemical energy storage materials in high performance supercapacitors is an essential step to promote the exploitation and utilization of magnesium resources in the field of energy storage. Unfortunately, the inherent chemical properties of magnesium lead to poor cycling stability and electrochemical reactivity, which seriously limit the application of Mg-based materials in supercapacitors. Herein, in this review, more than 70 research papers published in recent 10 years were collected and analyzed. Some representative research works were selected, and the results of various regulative strategies to improve the electrochemical performance of Mg-based materials were discussed. The effects of various regulative strategies (such as constructing nanostructures, synthesizing composites, defect engineering, and binder-free synthesis, etc.) on the electrochemical performance and their mechanism are demonstrated using spinel-structured MgX2O4 and layered structured Mg-X-LDHs as examples. In addition, the application of magnesium oxide and magnesium hydroxide in electrode materials, MXene's solid spacers and hard templates are introduced. Finally, the challenges and outlooks of Mg-based electrochemical energy storage materials in high performance supercapacitors are also discussed.

Abstract Background Cadmium (Cd) pollution in agricultural soils has become a priority environmental concern globally. A reasonable application of passivators is critical to address the problem. In this study, we examined the remediation effects of rice husk biochar (rBC) and sepiolite (Sep) as single and combined (rBC + Sep) treatments on Cd pollution in a weakly alkaline soil using three maize cultivars (Liyu 16, Zhengdan 958, and Sanbei 218) as test crops. We also explained the mechanisms involved in the remediation effects. Results The pseudo-second-order kinetic equation and Langmuir model could well describe the adsorption process of rBC + Sep for Cd2+. Compared with the control treatment (CK), soil available Cd concentration decreased by 29.51–36.34% under rBC + Sep treatment (p 0.05). Conclusions The application of 0.2% rBC + 0.5% Sep composite passivation material to weakly alkaline Cd-contaminated soil can effectively reduce the Cd concentration of soil and maize.

Abstract Background Diets low in vegetables are a main contributor to the health burden experienced by Australians living in rural communities. Given the ubiquity of smartphones and access to the Internet, digital interventions may offer an accessible delivery model for a dietary intervention in rural communities. However, no digital interventions to address low vegetable intake have been co-designed with adults living in rural areas. This paper describes the co-design of a digital intervention to improve vegetable intake with rural community members and research partners. Methods Active participants in the co-design process were adults ≥ 18 years living in three rural Australian communities (total n = 57) and research partners (n = 4) representing three local rural governments and one peak non-government health organisation. An iterative co-design process was undertaken to understand the needs (pre-design phase) and ideas (generative phase) of the target population. Eight online workshops and a community survey were conducted between July and December 2021. The MoSCoW prioritisation method was used to help participants identify the ‘Must-have, Should-have, Could-have, and Won’t-have or will not have right now’ features and functions of the digital intervention. Workshops were transcribed and inductively analysed using NVivo. Convergent and divergent themes were identified between the workshops and community survey to identify how to implement the digital intervention in the community. Results Consensus was reached on a concept for a digital intervention that addressed individual and food environment barriers to vegetable intake, specific to rural communities. Implementation recommendations centred on (i) food literacy approaches to improve skills via access to vegetable-rich recipes and healthy eating resources, (ii) access to personalisation options and behaviour change support, and (iii) improving the community food environment by providing information on and access to local food initiatives. Conclusions Rural-dwelling adults expressed preferences for personalised intervention features that can enhance food literacy and engagement with community food environments. This research will inform the development of the prototyping (evaluation phase) and feasibility testing (post-design phase) of this intervention.

The use of computer vision to estimate the Body Condition Score for cow has demonstrated to be feasible. However, most research has been limited to fixed camera positions, which restricts the technique’s usefulness. This research acquired cow data at various distances and angles to investigate the impact of distance and different depth images restoration method on scoring accuracy. A U-Net neural network-based model was employed for background segmentation. The model proposed in this study performs best among SegNet, UNet, UNet++ and DeeplabV3, with significant performance improvement and superior overall segmentation accuracy, and has stronger foreground object identification capability. Additionally, we utilize the concept of human feature point localization to pinpoint the positions of cow feature points. The results show that compared to Hourglass, CPN, and Hrnet, the model in this study has significant advantages in three core indicators: accuracy, recall, and mAP. Moreover, we presented an unsupervised depth image reconstruction model based on the Denoising Diffusion Probabilistic Model and Unet++ Mode, facilitating the measurement and scoring of cow characteristics. Finally, the measurement results of cow body size using the Lerp model, autoregressive model, GAN model, and the depth image completion model proposed in this study were compared. The method proposed in this study was found to be effective and feasible for meeting actual production requirements at a camera distance of 1–2 m from the cow, achieving high accuracy with a coefficient of determination above 0.9. Additionally, the three models used were effective in handling small-scale depth deficits, with a high degree of agreement between machine and manual measurements. The DDPM-based depth image reconstruction model was found to produce the most accurate results when the camera distance from the cow was between 1-3m. Therefore, this research makes it possible to make flexible measurements in the near range using existing methods. Accurate measurements at longer ranges are influenced by depth image quality and feature point localization accuracy, which require more advanced techniques for further investigation.

ABSTRACTThe evolution and future trajectory of island shorelines, amidst global climate change, are of increasing concern to governments, communities and researchers worldwide. However, the field of island studies is often hampered by a lack of data and inconsistent methodologies, leading to an inadequate understanding of the processes driving shoreline changes on islands within the context of climate change. This research aims to bridge this gap by analyzing islands in Southeast Asia, the Indian Ocean and the Mediterranean Sea from 1990 to 2020 using remote sensing. Of over 13,000 islands examined, approximately 12% experienced significant shifts in shoreline positions. The total shoreline length of these islands approaches 200,000 km, with 7.57% showing signs of landward erosion and 6.05% expanding seaward. Human activities, particularly reclamation and land filling, were identified as primary drivers of local shoreline transformations, while natural factors have a comparatively minor impact. Moreover, the ongoing rise in sea levels is identified as an exacerbating factor for coastal erosion rather than the primary cause. Drawing from these findings, we propose several adaptive measures for islands in response to climate change. Taken together, this research provides comprehensive data and a basis for decision-making for sustainable development of island territories.

Background: Lung adenocarcinoma (LUAD) is the commonest subtype of primary lung cancer. A comprehensive analysis of the association of immunity with amino acid metabolism in LUAD is critical for understanding the disease. Methods: The present study examined LUAD and noncancerous cases from the TCGA database. Differentially expressed genes (DEGs) between LUAD and noncancerous tissues were detected by analyzing processed expression profiles. We cross-referenced the up-regulated DEGs with Immune and Amino Acid Metabolism-related genes (I&AAMGs), resulting in Immune and Amino Acid Metabolism related differentially expressed genes (IAAAMRDEGs). The STRING database was employed to analyze PPI on IAAAMRDEGs, obtaining excavated hub genes, whose biological processes, molecular functions and cellular components were examined with GO/KEGG. Potential mechanisms related to LUAD were investigated by GSEA and GSVA. A prognostic model was built by LASSO-COX analysis, taking into consideration risk scores and prognostic factors to determine biomarkers affecting LUAD occurrence and prognosis. Results: Totally 377 genes were detected at the intersection of upregulated DEGs and I&AAMGs. Analysis of PPI on these 377 IAAAMRDEGs yielded 17 hub genes. A LASSO regression analysis was utilized to assess the prognostic values of the 17 hub genes. Validation using the combined dataset confirmed 4 genes, e.g., polo-like kinase (PLK1), Ribonucleotide Reductase Subunit M2 (RRM2), Thyroid Hormone Receptor Interactor 13 (TRIP13), and Hyaluronan-Mediated Motility Receptor (HHMR). The model's accuracy was further assessed by ROC curve analysis and the COX model. In addition, immunohistochemical staining obtained from the HPA database, revealed enhanced PLK1 expression in LUAD samples. Conclusion: LUAD pathogenesis is highly associated with immunity and amino acid metabolism. The PLK1, RRM2, TRIP13, and HMMR genes have prognostic values for LUAD. PLK1 upregulation in LUAD might be involved in tumorigenesis by modulating the cell cycle and represents a potential prognostic factor in clinic.

Abstract In nature, spider web is an interwoven network with high stability and elasticity from silk threads secreted by spider. Inspired by the structure of spider webs, light‐driven liquid crystal elastomer (LCE) active yarn is designed with super‐contractile and robust weavability. Herein, a novel biomimetic gold nanorods (AuNRs) @LCE yarn soft actuator with hierarchical structure is fabricated by a facile electrospinning and subsequent photocrosslinking strategies. Meanwhile, the inherent mechanism and actuation performances of the as‐prepared yarn actuator with interleaving network are systematically analyzed. Results demonstrate that thanks to the unique “like‐spider webs” structure between fibers, high molecular orientation within the LCE microfibers and good flexibility, they can generate super actuation strain (≈81%) and stable actuation performances. Importantly, benefit from the robust covalent bonding at the organic–inorganic interface, photopolymerizable AuNRs molecules are uniformly introduced into the polymer backbone of electrospun LCE yarn to achieve tailorable shape‐morphing under different light intensity stimulation. As a proof‐of‐concept illustration, light‐driven artificial muscles, micro swimmers, and hemostatic bandages are successfully constructed. The research disclosed herein can offer new insights into continuous production and development of LCE‐derived yarn actuator that are of paramount significance for many applications from smart fabrics to flexible wearable devices.

Adults with spinal cord injury (SCI), a destructive neurological injury, have a significantly higher incidence of osteoarthritis (OA), a highly prevalent chronic joint disorder. This study aimed to dissect the neuroimmune-related regulatory mechanisms of SCI and OA using bioinformatics analysis. Using microarray data from the Gene Expression Omnibus database, differentially expressed genes (DEGs) were screened between SCI and sham samples and between OA and control samples. Common DEGs were used to construct a protein-protein interaction (PPI) network. Weighted gene co-expression network analysis (WGCNA) was used to mine SCI- and OA-related modules. Shared miRNAs were identified, and target genes were predicted using the Human MicroRNA Disease Database (HMDD) database. A miRNA-gene-pathway regulatory network was constructed with overlapping genes, miRNAs, and significantly enriched pathways. Finally, the expression of the identified genes and miRNAs was verified using RT-qPCR. In both the SCI and OA groups, 185 common DEGs were identified, and three hub clusters were obtained from the PPI network. WGCNA revealed three SCI-related modules and two OA-related modules. There were 43 overlapping genes between the PPI network clusters and the WGCNA network modules. Seventeen miRNAs shared between patients with SCI and OA were identified. A regulatory network consisting of five genes, six miRNAs, and six signaling pathways was constructed. Upregulation of CD44, TGFBR1, CCR5, and IGF1, while lower levels of miR-125b-5p, miR-130a-3p, miR-16-5p, miR-204-5p, and miR-204-3p in both SCI and OA were successfully verified using RT-qPCR. Our study suggests that a miRNA-gene-pathway network is implicated in the neuroimmune-related regulatory mechanisms of SCI and OA. CD44, TGFBR1, CCR5, and IGF1, and their related miRNAs (miR-125b-5p, miR-130a-3p, miR-16-5p, miR-204-5p, and miR-204-3p) may serve as promising biomarkers and candidate therapeutic targets for SCI and OA.

BackgroundDiabetic foot complications impose a significant strain on healthcare systems worldwide, acting as a principal cause of morbidity and mortality in individuals with diabetes mellitus. While traditional methods in diagnosing and treating these conditions have faced limitations, the emergence of Machine Learning (ML) technologies heralds a new era, offering the promise of revolutionizing diabetic foot care through enhanced precision and tailored treatment strategies.ObjectiveThis review aims to explore the transformative impact of ML on managing diabetic foot complications, highlighting its potential to advance diagnostic accuracy and therapeutic approaches by leveraging developments in medical imaging, biomarker detection, and clinical biomechanics.MethodsA meticulous literature search was executed across PubMed, Scopus, and Google Scholar databases to identify pertinent articles published up to March 2024. The search strategy was carefully crafted, employing a combination of keywords such as “Machine Learning,” “Diabetic Foot,” “Diabetic Foot Ulcers,” “Diabetic Foot Care,” “Artificial Intelligence,” and “Predictive Modeling.” This review offers an in-depth analysis of the foundational principles and algorithms that constitute ML, placing a special emphasis on their relevance to the medical sciences, particularly within the specialized domain of diabetic foot pathology. Through the incorporation of illustrative case studies and schematic diagrams, the review endeavors to elucidate the intricate computational methodologies involved.ResultsML has proven to be invaluable in deriving critical insights from complex datasets, enhancing both the diagnostic precision and therapeutic planning for diabetic foot management. This review highlights the efficacy of ML in clinical decision-making, underscored by comparative analyses of ML algorithms in prognostic assessments and diagnostic applications within diabetic foot care.ConclusionThe review culminates in a prospective assessment of the trajectory of ML applications in the realm of diabetic foot care. We believe that despite challenges such as computational limitations and ethical considerations, ML remains at the forefront of revolutionizing treatment paradigms for the management of diabetic foot complications that are globally applicable and precision-oriented. This technological evolution heralds unprecedented possibilities for treatment and opportunities for enhancing patient care.

Genetic diseases are currently diagnosed by functional mutations. However, only some mutations are associated with disease. It is necessary to establish a quick prediction model for clinical screening. Pathogenic mutations in NGLY1 cause a rare autosomal recessive disease known as congenital disorder of deglycosylation (NGLY1-CDDG). Although NGLY1-CDDG can be diagnosed through gene sequencing, clinical relevance of a detected mutation in NGLY1 needs to be further confirmed. In this study, taken NGLY1-CDDG as an example, a comprehensive and practical predictive model for pathogenic mutations on NGLY1 through an NGLY1/Glycopeptide complex model was constructed, the binding sites of NGLY1 and glycopeptides were simulated, and an in vitro enzymatic assay system was established to facilitate quick clinical decisions for NGLY1-CDDG patients. The docking model covers 42 % of reported NGLY1-CDDG missense mutations (5/12). All reported mutations were subjected to in vitro enzymatic assay in which 18 mutations were dysfunctional (18/30). In addition, a full spectrum of functional R328 mutations was assayed and 11 mutations were dysfunctional (11/19). In this study, a model of NGLY1 and glycopeptides was built for potential functional mutations in NGLY1. In addition, the effect of potential regulatory compounds, including N-acetyl-l-cysteine and dithiothreitol, on NGLY1 was examined. The established in vitro assay may serve as a standard protocol to facilitate rapid diagnosis of all mutations in NGLY1-CDDG. This method could also be applied as a comprehensive and practical predictive model for the other rare genetic diseases.

The improved electronic conductivity and ion diffusion efficiency of TiO2‐based anode materials have been extensively studied by introducing oxygen vacancies or creating amorphous structure. There has been little exploration of the synergistic effects by combining these two modification strategies into one TiO2‐based matrix. In addition, the structure–activity relationship and energy storage mechanism involved remain to be understood. Herein, a facile one‐step coreduction method is reported to successfully produce the oxygen vacancy‐doped amorphous TiO2 nanoparticles. The oxygen vacancy‐doped amorphous TiO2 anode exhibits significantly enhanced electrochemical activity and high‐rate stability (up to 87 mAh g−1 over 10 000 discharge/charge cycles at a current rate of 100 C). This outstanding electrochemical performance is attributable to the synergistic effects of amorphous structure and oxygen vacancies. Density functional theory calculations reveal the enhanced electronic conductivity and thermodynamically favorable lithium insertion architecture due to the introduction of oxygen vacancy and the construction of the amorphous skeleton. Dynamic analysis indicates that the lithium‐storage mechanism is a hybrid of surface capacitive storage and enhanced diffusion‐controlled ion insertion. This work opens up new pathways in developing novel anode materials for efficient energy storage from the wide spectrum of metal oxides.

IntroductionNurses caring for patients with gynecological cancer experience significant job stress, which adversely impacts their mental health. Previous studies have indicated that perceived professional benefits serves as a protective factor for nurses’ mental health, and factors such as job stress, perceived social support and self-efficacy influence their perceived professional benefits. However, the relationships between these factors and the associated mechanisms have remained incompletely understood. This study explored the role of perceived social support and self-efficacy in job stress and perceived professional benefits among nurses caring for patients with gynecological cancer.MethodsDuring June and July 2023, an investigation was conducted in Anhui Province. The Nurse Job Stressors Scale, Perceived Social Support Scale, Nurses’ Perceived Professional Benefits Questionnaire and General Self-Efficacy Scale were administered to 311 nurses caring for patients with gynecological cancer. A chained-mediated effect model was constructed and validated.ResultsJob stress negatively affected nurses’ perceived professional benefits. Perceived social support was a mediator in job stress and nurses’ perceived professional benefits, with a mediating effect value of −0.093. Additionally, perceived social support and self-efficacy functioned as sequential mediators in this relationship, with a mediating effect value of −0.032.ConclusionThis study unveils the influencing mechanisms of job stress on perceived professional benefits of nurses caring for patients with gynecological cancer. It is essential for nursing managers to alleviate nurses’ job stress, provide sufficient and effective social support and improve their self-efficacy, ultimately enhancing their perceived professional benefits.

High traffic flow in a confined tunnel makes fire safety a critical issue. This paper proposed a digital twin framework for tunnel fire safety management in real-time, driven by dynamic sensor data and AIoT technologies. A deep learning model trained by the Transformer network and simulation dataset is used to predict real-time fire location and size. Then, the AI model is integrated into a 3D digital twin platform developed by the game engine Unity 3D. The performance of the proposed digital twin framework is demonstrated using numerical experiments and large-scale tunnel fire tests. Results show that the established AI model achieved promising accuracy in predicting fire location and power for both numerical and experimental data. The digital twin platform can also visualize the 3D fire scene that supports evacuation, firefighting, and emergency rescue. This research demonstrates the feasibility of using a 3D environment and digital twin in real-time fire safety management.

The perioperative neurocognitive disorder (PND) is a severe complication that affects millions of surgical patients each year. Homocysteine (Hcy) is known to increase the risk of developing PND in both young and elderly mice. However, whether Hcy alone can induce cognitive deficits in middle-aged mice (12-month-old), whether exercise can attenuate Hcy-induced hippocampus-related cognitive deficits after surgery through suppressing neuroinflammation, synaptic elimination, and the level of Hcy remains unknown. The present study aimed to answer these questions through testing the possibility of establishing a PND model using 12-month-old mice which received homocysteine injections before exploratory laparotomy and the therapeutic mechanism of exercise. In the present study, it was found that levels of serum homocysteine were age-dependently increased in mice with a significant difference between that of 18-month-old mice and 6-week, 6-month, and 12-month-old mice. PND occurred in 18-month but not in 12-month-old mice after exploratory laparotomy under isoflurane anesthesia. Intraperitoneal injection of Hcy for 3 consecutive days before surgery rendered 12-month-old mice to develop PND after abdominal laparotomy under isoflurane anesthesia at a minimal dosage of 20 mg/kg. Neuroinflammation and synaptic elimination was present in 12-month-old preoperative Hcy-injected mice. Preoperative voluntary wheel exercise could prevent PND in 12-month-old mice that have received Hcy injection before surgery, which might be related to the decreased level of serum Hcy. Activation of glial cells, proinflammatory phenotype markers and synaptic elimination were attenuated in the hippocampus of 12-month-old preoperative Hcy-injected mice by this exercise. These results provide direct evidence that hyperhomocysteinemia can induce postoperative cognitive deficits in middle-aged mice. Pre-surgery exercise can effectively prevent Hcy-precipitated postoperative cognitive dysfunction.

Single-cell sequencing is a novel and rapidly advancing high-throughput technique that can be used to investigating genomics, transcriptomics, and epigenetics at a single-cell level. Currently, single-cell sequencing can not only be used to draw the pancreatic islet cells map and uncover the characteristics of cellular heterogeneity in type 2 diabetes, but can also be used to label and purify functional beta cells in pancreatic stem cells, improving stem cells and islet organoids therapies. In addition, this technology helps to analyze islet cell dedifferentiation and can be applied to the treatment of type 2 diabetes. In this review, we summarize the development and process of single-cell sequencing, describe the potential applications of single-cell sequencing in the field of type 2 diabetes, and discuss the prospects and limitations of single-cell sequencing to provide a new direction for exploring the pathogenesis of type 2 diabetes and finding therapeutic targets.

Abstract Background Severe combined immunodeficiency (SCID) is a group of fatal primary immunodeficiencies characterized by the severe impairment of T-cell differentiation. IL7R deficiency is a rare form of SCID that usually presents in the first months of life with severe and opportunistic infections, failure to thrive, and a high risk of mortality unless treated. Although recent improvements in early diagnosis have been achieved through newborn screening, few IL7R-related SCID patients had been reported in the Chinese population. Case presentation Here, we retrospectively analyzed a case of SCID in a 5-month-old girl with symptoms, including severe T-cell depletion, recurrent fever, oral ulcers, pneumonia, hepatosplenomegaly, bone marrow hemophagocytosis, and bacterial and viral infections. Whole-exome sequencing (WES), quantitative PCR (qPCR), and chromosome microarray analysis (CMA) were performed to identify the patient’s genetic etiology. We identified a 268 kb deletion and a splicing variant, c.221 + 1G > A, in the proband. These two variants of IL7R were inherited from the father and mother. Conclusions To our knowledge, this is the first report of whole IL7R gene deletion in combination with a pathogenic splicing variant in a patient with SCID. This deletion also expands the pathogenic variation spectrum of SCID caused by IL7R. The incorporation of exome-based copy number variant analysis makes WES a powerful molecular diagnostic technique for the clinical diagnosis of pediatric patients.

Poultry semen cryopreservation technology is one of the most direct methods to protect poultry germplasm, and in this study, the back and abdomen massage method is used to collect the semen of 20 Huoyan male geese, which is on the basis of EK diluent adding different combinations of dimethyl sulfoxide (DMSO) and trehalose, in total 7 different combinations treatments were achieved: D1T0 (5%DMSO), D1T1 (5% DMSO + 50 mM trehalose), D1T2 (5%DMSO + 100 mM trehalose), D2T0 (10% DMSO), D2T1 (10% DMSO + 50 mM trehalose), D2T2 (10% DMSO + 100 mol trehalose) and no addition group D0T0 (0% DMSO + 0 mM trehalose). Diluted semen was frozen in granules in liquid nitrogen vapour. After thawing in 40°C water bath, determinate sperm livability, acrosome integrity, plasma membrane integrity, catalase (CAT) activity, superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) activity, malondialdehyde (MDA) content and reactive oxygen species (ROS) level, and the results showed that 10% DMSO and 0.05 mol/L trehalose could significantly improve the sperm motility, acrosome integrity rate and plasma membrane integrity rate after thawing, and significantly increase the levels of antioxidant enzymes CAT, SOD and GSH-Px in seminal plasma (P

Abstract Objectives The OPG/RANKL signal pathway was important regulation mechanism of bone remodeling cycle, but the effect of osteoprotegerin (OPG) and RANKL in osteoporosis was uncertain. We did a systematic review with meta-analysis to assess the association between serum OPG/RANKL and osteoporosis. Methods The systematic search, data extraction, critical appraisal, and meta-analysis were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Randomized controlled studies were searched in PubMed, OvidMedline, Embase (1946 to present). Standard mean difference (SMD), and associated credible interval (CI) were calculated using RevMan statistical software to assess the continuous data. Heterogeneity in studies was measured by I 2 values. Subgroup analysis was performed based on different bone turnover. Results A total of 5 randomized controlled studies met the inclusion criteria. Both OPG and RANKL had no significant differences between the osteoporosis and control group, and the statistical heterogeneity was high in meta-analysis. However, RANKL had significant differences between the osteoporosis group with low bone turnover and control group (SMD = − 1.17; 95% CI − 1.77 to 0.57; P value